The roles of ZFAT in thymocyte differentiation and homeostasis of peripheral naive T-cells.

ZFAT (zinc-finger gene in AITD susceptibility region), originally identified as a candidate susceptibility gene for autoimmune thyroid disease, has been reported to be involved in various cellular processes and several common diseases including multiple sclerosis. Recent studies revealed that mouse Zfat is a novel critical regulator for both thymocyte differentiation and peripheral T-cell homeostasis. Zfat deficiency at early thymocyte developmental stages results in the inhibition of the development of CD4(+)CD8(+) thymocytes with an impaired positive selection. Zfat deficiency in peripheral T-cells results in a reduction in the number of T-cells with decreased expression of the interleukin-7 receptor-α (IL-7Rα) that is critical for T-cell homeostasis. In addition, T-cell antigen receptor stimulation-induced responses of Zfat-deficient T-cells are also impaired, with reduced IL-2Rα expression. This review highlights and discusses the roles of Zfat in thymocyte differentiation of T-cells and in the homeostasis of naive T-cells with recent work.